CA1043257A - Antibacterially active combinations - Google Patents
Antibacterially active combinationsInfo
- Publication number
- CA1043257A CA1043257A CA215,752A CA215752A CA1043257A CA 1043257 A CA1043257 A CA 1043257A CA 215752 A CA215752 A CA 215752A CA 1043257 A CA1043257 A CA 1043257A
- Authority
- CA
- Canada
- Prior art keywords
- sulphonamide
- potentiator
- diamino
- amino
- pyrimidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
Antibacterially active compositions containing a sulfonamide of the formula (I) or a physiologically acceptable salt thereof with a strong base and a poten-tiator which is a 2,4-diamino-5-benzylpyrimidine of the formula
Antibacterially active compositions containing a sulfonamide of the formula (I) or a physiologically acceptable salt thereof with a strong base and a poten-tiator which is a 2,4-diamino-5-benzylpyrimidine of the formula
Description
1~343257 The present invention is concerned with anti~acterial compositions .
and a process for the manufacture thereof. .
The antibacterial compositions provided by the present invention ..
contain the sulphonamide of the formula 2N ~ ~ 52NH ~ N - C2U5 (1) or a physiologically acceptable salt thereof with a strong base and a sulphon-amide potentiator which is a 2,4-diamino-5-benzyl-pyrimidine of the general :
formula ~.
U2 ~ \ ~ CU2 ~ R ~II) N~2 R2 ~:
, wherein Rl represents a lower alkoxy group, R2 represents a lower alkoxy group and R3 represents an amino, ~lower alkyl)-amino, di~lower alkyl)amino .
or lower alkoxy group, or a physiologically acceptable acid addition salt thereof, wherein th0 weight ratio of sulphonamide to sulphonamide potentiator amounts to from 1:1 to 40~
According to the present invention, there is also provided a process ~:.
or the manufacture of an antibacterial composition as disclosed above which process comprises mixing together the sulphonamide of formula I as previously `:
defined, or a physiologically acceptable salt thereof with a strong base, and ~ .
a sulphonamide potentiator as previously defined, to produce a composition 20. in which the weight ratio of sulphonamide to sulphonamide potentiator amounts ::~
to from 1:1 to 40:1.
The invention further provides a pharmaceutical preparation which :
contains the sulphonamide of the formula ~;` ~. ' '. ~-''"' ,$~
. ~
~ -2- - :
1~43Z57 :: ~
.
~ ~ 2 ~ ~ ---C2l5 or a physiologically acceptable salt thereof with a strong base and a sulphon-amide potentiator as previously defined, in a weight ratio of sulphonamide to sulphonamide potentiator of from 1:1 to 40:1, together with a compatible pharmaceutical carrier material and, a process for the manufacture of such a pharmaceutical preparation~ which process comprises mixing an antibac~erial -composition as previously defined or the individual ingredients thereof with a compatible pharmaceutical carrier material. ~ -The compound of formula I is a known compound having antibacterial activity. It has been found that by the addition of a sulphonamide poten-tiator the chemotherapeutic activity and especially the antibaterial activity in the urine of the compound of formula I and its salts can be increased to a surprising ext0nt. ;~
As used in this description and in the accompanying claimsJ the ~ ;
terms "lower alkyl" and "lower alkoxy" include straight-chain and branched- ;
chain alkyl and alkoxy groups which preferably contain up to 7, especially ;
from l to 4, carbon atoms such as the methyl, methoxy, ethyl, ethoxy, propyl, propoxy, isopropyl, isopropoxy, butyl, isobutyl, tert.-butyl, isobutoxy and tertO-butoxy groups. A preferred lower alkoxy group is the methoxy group.
" '':` '' '~'''~ ;''',' ' ,, :', -2a-1~)43ZS7 : ~
Especially preferred 2,4-diamino-5-benzyl-pyrimidines of formula II are 2,4-diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidine and 2,4-diamino-5-~4-amino-3,5-dimethoxybenzyl)-pyrimidine. .
The 2,4-diamino-5-benzyl-pyrimidines of formula II, insofar as they are not known, can be prepared either in a manner known per se or, for example, by chlorinating or brominating a compound of the general formula Rl H2N ~ ~ C~2 ~ ~ R4 (111) ~ ~
OH R2 .
':'".'. ' . , ' '' " ' ~ -, ~,. .
.,~i ~ :
'1~43Z57 :
, wherein R4 represents an ~mino, (lower alkyl)amino or di(lower alkyl)amino group and Rl and R2 have the signific~nce given earlier, in a m~ner known per se and reacting ths resultin~ h~lo compound with ammonia. The reaction with ammonia is expediently carried out in alkanolic, especially meth~nolic, solution at a temperature between 80C and 200C, pre~erably between about 100C and 150C. Since these temperatures lie ;-above the boiling point of methanol, the reaction is carried out in a closed system (e.g. in an autoclave).
Physiologically acceptable acid addition salts of 2,4--diamino-5-benzyl-pyrimidines of formula II can be prepared using convenbional inorganic and organic acids such as, ~or ex~mple, hydrochlorio acid, sulphuric acid, pho~phoric acid, formic aoid, acetic acid, malonic acid, succinic acid, malic i i acid, citric acid, tartaric acid, maloic acid, fumaric acid, methanesulphonic acid and p-toluenesulphonic acid, As physiologically acceptable strong bases for the `~
preparation of salts o~ N-sulphanilyl-l-ethylcytosine of formula I there can be used conventional inorganic and or~anic base~, e~pecially alkali metal hydroxides and alkanol-amines such a ethanolamine.
A Os~h~4~ he weight ratio of sulphonamide to sulphonamide potentiator in the antibacterial compositions provided by the present invention expedien-tly amounts to l:l to 40:1, -- 4 _ ;~i.
,. . . ~ .
. ' ~ ' , , . . . ' 1~43ZS7 preferably 5:1. The present antibacterial compositions include not only mixtures which conRist 801ely of the two active in~redients, n~mely the ~ulphonamide and the sulphon-P~ide potentiator, but al~o mixtures which contain one or more additional substances.
~he process provided by the present invention for the manufacture of the antibacterial compositions aforesaid -compri~es mixing the sulphonamide ingredient with the sulphon- -~
amide potentiator in6redient, the sulphon~m;de and the sulphonamide potentiator being expediently used in a weight ratio of from 1:1 to 40:1, preferably 5~ he process ca~
be carried out in a manner known per se.
~he antiba¢terial compositlons provided by the present inventlon, whioh pos~ess a good toleran¢e or a slight -~
toxioity, ar~ active againat gram-positive and gr~m negative baateria ~uch a~ ooli and Proteus baailli, Xlebgi~llae, Aeroba¢ter and Enterococai. ~hey are especially aative, for example, against Escherichia coli, Proteus vulgaris, Proteus mirabilis, Kleb~iella pneumoniae, Aerobacter aerogenes snd Streptococcus faecalis. ~hey are accordingly ~uitable for combating and preventing bacterial inrections, especially the ~o-called cavity infections ~uch as infections of the urinary tract. ~he administration of the pre~ent anti-bacterial compositions can be carried out orally or parenterally.
When 200 mg/kg of a 5:1 mixture of ~-~ulphanilyl-l--eth~lcytosine and 2,4-diamino-5-(3,4,5-trimethoxybenzyl)-.. . . .
. - _ 5 _ -pyrimidine were administered orally to rats a very good activity was observed. The activity, measured in urine, of this combination a~ainst E. coli is, for example, 92 times greater than that of 200 mg/kg of ~-(5-nitro-2-furfuryliden)--l-amino-hydantoin and 203 ~imes greater than that of the correspondin~ amount (namely 167 mg/kg) of the unpotent$ated N-sulphanilyl-l-ethylcgtosine.
The antibacterial compo~itions provided by the pre3ent inventio~ can be administered in the form of pharm~ceutical preparations which contain an organic or inorganic, inert carrier material suitable for oral or parenteral administration such as, for example, water, gelatine, gum arabic, lactose, starch, magnesium stearate, talc, ~e~etable oils, poly-alkylene~lycols, petroleum ~ally etc. ~he pharmaceutical preparations can be made up in a solid form (e.~. as tablets, draEées, ~uppositorie~ or capsules) or in a liquid form (e.g.
as ~olutions, sucpensions or emulsions). ~hey may be ~terilised and/or may contain ad~uvants such as preservati~es, stabilisers, wettin~ agents, emulsifiers, salts for varying the osmotic pres~ure or buffexs.
~he preparation of the pharmaceutical preparations can `
be carried out in a manner known per se.
........
A tablet suitable for use in human medicine can, for example, contain 400 mg of N-sulphanilyl-l-ethylcytosine and 80 mg of 2,4-diamino-5-(3,4~5-trimethoxybenzyl)-pyrimidine and a tablet for children can contain 5~/o of each of these :, . . .
- 6 - `
amounts. ~he dose administered daily can be, or has to be, suited to i~dividual requirements a~d varied within wide limits.
_ 7 _ ~ .
. .
1~4~3Z57 ~he following Example~ illu~trate the present invention:
Medicinal preparations containing N-sulphanilyl-l--ethylcytosine and 2,4-di~mino-5-(314~5 trimethoxybenzyl)--pyrimidine in a weight ratio of 5:1 (active ingredient).
.:
a) ~ablets:
Aotive ingredient480 m~ 240 mg Mannitol - 50 mg ~actofe 30 mg 50 mg q 10 Avicel ~ 120 mg 147 m6 ~lose~ 5 m4 ~ m~
~al¢ 14 mg 9 mg Magnesium stearat~1 mg 1 mg .
650 m~ 5O m4 . ..
.. ..
~fhe a¢tive i~4redient is mixed with a portion of the :
~vicel, lactose and, optionally, maize star¢h. ~fhe mixture is granulated w~th a~ a~ueous or al¢oholic~agueou~f ~ylose~
solution a~d dri~d and, after the addition of the remainin~
ingredients, praf3sed to tablets.
, b) Injefotion ffolution in 5 ml ampoules:
Active ingredient 480.0 m4 480.0 mg I Sodium hydroxide 59.1 mg -f Diethanolamine - 155.4 mg l ~ Water for in~ection purposes ad 5 ml ~:
, ~ tr~ K
..
- 8 - .
~043ZS7 ~he ampoules are filled under nitrogen and sterilised in an autoclave at 120C.
c) Cap~ules:
Active ingredient240.0 mg480 mg Methylcellulo~e2.5 mg 5 mg Talc 4.0 mg 8 mg Primojel~ 7.5 mg 15 mg Magnesium stearate 1.0 mg 2 mg 255.0 mg 510 mg ~he active ingredient i8 moistened with a methylcellulose solution and kneaded. ~he mass is then granulated, dried and sieved. A mixture of Primojel, talc and magnesium stearate is mixed with the granulate. Filling into inter-locking gelatine capsules i~ carried out on an automatic capsule ~illing machine.
Example 2 Medicinal preparations containing N-sulphanilyl-l--ethylcytosine and 2,4-diamino-5-(4-amino-3?5-dimethoxybenzyl)--p~rimidine in a weight ratio of 5:1 (active ingredient).
" ' a) ~ablets:
Active ingredient500 mg 250 mg .
Mannitol 30 mg 30 mg Maize ~tarch 50 mg 30 mg I Talc 18 mg 9 mg 1 25 Magnesium stearate 2 mg 1 mg 600 m~ 320 mg ~rade~K
_ 9_ 1.. ,.. ,., " .. ..
~04~Z57 -~he active ingredient is mixed with the mannitol and portion of the maize starch, moistened with a m~ize starch paste and kneaded. ~he mass i8 then granulated, dried and sieved and, after the addition of the remaining ingredients, can be pressed to tablet~.
b) Capsules:
Active ingredient500 mg 250 mg Pharmacoat 603 5 mg 3 mg -~
Primo~elk 10 mg 7 mg ~alc 9 mg 9 mg Magne~ium stearate1 mg 1 mg 525 mg 270 mg .....
, . : . . .
~he active in~redient i8 moi~tened with an aqueous Pharmaooat~solution and kneaded. ~he mass is then granulated, dried and si~e~ and, after the addition of the remaining in~redient~, i5 ready for rilling into oapsule~ on an automatic oap~ule ~illin6 machine.
' 3~ ~r~ ~Ar~<
:, ... .
'.
, ~.' - - 10 - .-.
and a process for the manufacture thereof. .
The antibacterial compositions provided by the present invention ..
contain the sulphonamide of the formula 2N ~ ~ 52NH ~ N - C2U5 (1) or a physiologically acceptable salt thereof with a strong base and a sulphon-amide potentiator which is a 2,4-diamino-5-benzyl-pyrimidine of the general :
formula ~.
U2 ~ \ ~ CU2 ~ R ~II) N~2 R2 ~:
, wherein Rl represents a lower alkoxy group, R2 represents a lower alkoxy group and R3 represents an amino, ~lower alkyl)-amino, di~lower alkyl)amino .
or lower alkoxy group, or a physiologically acceptable acid addition salt thereof, wherein th0 weight ratio of sulphonamide to sulphonamide potentiator amounts to from 1:1 to 40~
According to the present invention, there is also provided a process ~:.
or the manufacture of an antibacterial composition as disclosed above which process comprises mixing together the sulphonamide of formula I as previously `:
defined, or a physiologically acceptable salt thereof with a strong base, and ~ .
a sulphonamide potentiator as previously defined, to produce a composition 20. in which the weight ratio of sulphonamide to sulphonamide potentiator amounts ::~
to from 1:1 to 40:1.
The invention further provides a pharmaceutical preparation which :
contains the sulphonamide of the formula ~;` ~. ' '. ~-''"' ,$~
. ~
~ -2- - :
1~43Z57 :: ~
.
~ ~ 2 ~ ~ ---C2l5 or a physiologically acceptable salt thereof with a strong base and a sulphon-amide potentiator as previously defined, in a weight ratio of sulphonamide to sulphonamide potentiator of from 1:1 to 40:1, together with a compatible pharmaceutical carrier material and, a process for the manufacture of such a pharmaceutical preparation~ which process comprises mixing an antibac~erial -composition as previously defined or the individual ingredients thereof with a compatible pharmaceutical carrier material. ~ -The compound of formula I is a known compound having antibacterial activity. It has been found that by the addition of a sulphonamide poten-tiator the chemotherapeutic activity and especially the antibaterial activity in the urine of the compound of formula I and its salts can be increased to a surprising ext0nt. ;~
As used in this description and in the accompanying claimsJ the ~ ;
terms "lower alkyl" and "lower alkoxy" include straight-chain and branched- ;
chain alkyl and alkoxy groups which preferably contain up to 7, especially ;
from l to 4, carbon atoms such as the methyl, methoxy, ethyl, ethoxy, propyl, propoxy, isopropyl, isopropoxy, butyl, isobutyl, tert.-butyl, isobutoxy and tertO-butoxy groups. A preferred lower alkoxy group is the methoxy group.
" '':` '' '~'''~ ;''',' ' ,, :', -2a-1~)43ZS7 : ~
Especially preferred 2,4-diamino-5-benzyl-pyrimidines of formula II are 2,4-diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidine and 2,4-diamino-5-~4-amino-3,5-dimethoxybenzyl)-pyrimidine. .
The 2,4-diamino-5-benzyl-pyrimidines of formula II, insofar as they are not known, can be prepared either in a manner known per se or, for example, by chlorinating or brominating a compound of the general formula Rl H2N ~ ~ C~2 ~ ~ R4 (111) ~ ~
OH R2 .
':'".'. ' . , ' '' " ' ~ -, ~,. .
.,~i ~ :
'1~43Z57 :
, wherein R4 represents an ~mino, (lower alkyl)amino or di(lower alkyl)amino group and Rl and R2 have the signific~nce given earlier, in a m~ner known per se and reacting ths resultin~ h~lo compound with ammonia. The reaction with ammonia is expediently carried out in alkanolic, especially meth~nolic, solution at a temperature between 80C and 200C, pre~erably between about 100C and 150C. Since these temperatures lie ;-above the boiling point of methanol, the reaction is carried out in a closed system (e.g. in an autoclave).
Physiologically acceptable acid addition salts of 2,4--diamino-5-benzyl-pyrimidines of formula II can be prepared using convenbional inorganic and organic acids such as, ~or ex~mple, hydrochlorio acid, sulphuric acid, pho~phoric acid, formic aoid, acetic acid, malonic acid, succinic acid, malic i i acid, citric acid, tartaric acid, maloic acid, fumaric acid, methanesulphonic acid and p-toluenesulphonic acid, As physiologically acceptable strong bases for the `~
preparation of salts o~ N-sulphanilyl-l-ethylcytosine of formula I there can be used conventional inorganic and or~anic base~, e~pecially alkali metal hydroxides and alkanol-amines such a ethanolamine.
A Os~h~4~ he weight ratio of sulphonamide to sulphonamide potentiator in the antibacterial compositions provided by the present invention expedien-tly amounts to l:l to 40:1, -- 4 _ ;~i.
,. . . ~ .
. ' ~ ' , , . . . ' 1~43ZS7 preferably 5:1. The present antibacterial compositions include not only mixtures which conRist 801ely of the two active in~redients, n~mely the ~ulphonamide and the sulphon-P~ide potentiator, but al~o mixtures which contain one or more additional substances.
~he process provided by the present invention for the manufacture of the antibacterial compositions aforesaid -compri~es mixing the sulphonamide ingredient with the sulphon- -~
amide potentiator in6redient, the sulphon~m;de and the sulphonamide potentiator being expediently used in a weight ratio of from 1:1 to 40:1, preferably 5~ he process ca~
be carried out in a manner known per se.
~he antiba¢terial compositlons provided by the present inventlon, whioh pos~ess a good toleran¢e or a slight -~
toxioity, ar~ active againat gram-positive and gr~m negative baateria ~uch a~ ooli and Proteus baailli, Xlebgi~llae, Aeroba¢ter and Enterococai. ~hey are especially aative, for example, against Escherichia coli, Proteus vulgaris, Proteus mirabilis, Kleb~iella pneumoniae, Aerobacter aerogenes snd Streptococcus faecalis. ~hey are accordingly ~uitable for combating and preventing bacterial inrections, especially the ~o-called cavity infections ~uch as infections of the urinary tract. ~he administration of the pre~ent anti-bacterial compositions can be carried out orally or parenterally.
When 200 mg/kg of a 5:1 mixture of ~-~ulphanilyl-l--eth~lcytosine and 2,4-diamino-5-(3,4,5-trimethoxybenzyl)-.. . . .
. - _ 5 _ -pyrimidine were administered orally to rats a very good activity was observed. The activity, measured in urine, of this combination a~ainst E. coli is, for example, 92 times greater than that of 200 mg/kg of ~-(5-nitro-2-furfuryliden)--l-amino-hydantoin and 203 ~imes greater than that of the correspondin~ amount (namely 167 mg/kg) of the unpotent$ated N-sulphanilyl-l-ethylcgtosine.
The antibacterial compo~itions provided by the pre3ent inventio~ can be administered in the form of pharm~ceutical preparations which contain an organic or inorganic, inert carrier material suitable for oral or parenteral administration such as, for example, water, gelatine, gum arabic, lactose, starch, magnesium stearate, talc, ~e~etable oils, poly-alkylene~lycols, petroleum ~ally etc. ~he pharmaceutical preparations can be made up in a solid form (e.~. as tablets, draEées, ~uppositorie~ or capsules) or in a liquid form (e.g.
as ~olutions, sucpensions or emulsions). ~hey may be ~terilised and/or may contain ad~uvants such as preservati~es, stabilisers, wettin~ agents, emulsifiers, salts for varying the osmotic pres~ure or buffexs.
~he preparation of the pharmaceutical preparations can `
be carried out in a manner known per se.
........
A tablet suitable for use in human medicine can, for example, contain 400 mg of N-sulphanilyl-l-ethylcytosine and 80 mg of 2,4-diamino-5-(3,4~5-trimethoxybenzyl)-pyrimidine and a tablet for children can contain 5~/o of each of these :, . . .
- 6 - `
amounts. ~he dose administered daily can be, or has to be, suited to i~dividual requirements a~d varied within wide limits.
_ 7 _ ~ .
. .
1~4~3Z57 ~he following Example~ illu~trate the present invention:
Medicinal preparations containing N-sulphanilyl-l--ethylcytosine and 2,4-di~mino-5-(314~5 trimethoxybenzyl)--pyrimidine in a weight ratio of 5:1 (active ingredient).
.:
a) ~ablets:
Aotive ingredient480 m~ 240 mg Mannitol - 50 mg ~actofe 30 mg 50 mg q 10 Avicel ~ 120 mg 147 m6 ~lose~ 5 m4 ~ m~
~al¢ 14 mg 9 mg Magnesium stearat~1 mg 1 mg .
650 m~ 5O m4 . ..
.. ..
~fhe a¢tive i~4redient is mixed with a portion of the :
~vicel, lactose and, optionally, maize star¢h. ~fhe mixture is granulated w~th a~ a~ueous or al¢oholic~agueou~f ~ylose~
solution a~d dri~d and, after the addition of the remainin~
ingredients, praf3sed to tablets.
, b) Injefotion ffolution in 5 ml ampoules:
Active ingredient 480.0 m4 480.0 mg I Sodium hydroxide 59.1 mg -f Diethanolamine - 155.4 mg l ~ Water for in~ection purposes ad 5 ml ~:
, ~ tr~ K
..
- 8 - .
~043ZS7 ~he ampoules are filled under nitrogen and sterilised in an autoclave at 120C.
c) Cap~ules:
Active ingredient240.0 mg480 mg Methylcellulo~e2.5 mg 5 mg Talc 4.0 mg 8 mg Primojel~ 7.5 mg 15 mg Magnesium stearate 1.0 mg 2 mg 255.0 mg 510 mg ~he active ingredient i8 moistened with a methylcellulose solution and kneaded. ~he mass is then granulated, dried and sieved. A mixture of Primojel, talc and magnesium stearate is mixed with the granulate. Filling into inter-locking gelatine capsules i~ carried out on an automatic capsule ~illing machine.
Example 2 Medicinal preparations containing N-sulphanilyl-l--ethylcytosine and 2,4-diamino-5-(4-amino-3?5-dimethoxybenzyl)--p~rimidine in a weight ratio of 5:1 (active ingredient).
" ' a) ~ablets:
Active ingredient500 mg 250 mg .
Mannitol 30 mg 30 mg Maize ~tarch 50 mg 30 mg I Talc 18 mg 9 mg 1 25 Magnesium stearate 2 mg 1 mg 600 m~ 320 mg ~rade~K
_ 9_ 1.. ,.. ,., " .. ..
~04~Z57 -~he active ingredient is mixed with the mannitol and portion of the maize starch, moistened with a m~ize starch paste and kneaded. ~he mass i8 then granulated, dried and sieved and, after the addition of the remaining ingredients, can be pressed to tablet~.
b) Capsules:
Active ingredient500 mg 250 mg Pharmacoat 603 5 mg 3 mg -~
Primo~elk 10 mg 7 mg ~alc 9 mg 9 mg Magne~ium stearate1 mg 1 mg 525 mg 270 mg .....
, . : . . .
~he active in~redient i8 moi~tened with an aqueous Pharmaooat~solution and kneaded. ~he mass is then granulated, dried and si~e~ and, after the addition of the remaining in~redient~, i5 ready for rilling into oapsule~ on an automatic oap~ule ~illin6 machine.
' 3~ ~r~ ~Ar~<
:, ... .
'.
, ~.' - - 10 - .-.
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. An antibacterial composition containing the sulphonamide of the formula or a physiologically acceptable salt thereof with a strong base and a sulphon-amide potentiator, which is a 2,4-diamino-5-benzyl-pyrimidine of the general formula (II) , wherein R1 represents a lower alkoxy group, R2 represents a lower alkoxy group and R3 represents an amino, (lower alkyl)-amino, di(lower alkyl)amino or lower alkoxy group, or a physiologically acceptable acid addition salt thereof, wherein the weight ratio of sulphonamide to sulphonamide potentiator amounts to from 1:1 to 40:1.
2. A composition according to claim 1, wherein said 2,4-diamino-5-benzyl-pyrimidine is 2,4-diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidine.
3. A composition according to claim 1, wherein said 2,4-diamino-5-benzyl-pyrimidine is 2,4-diamino-5-(4-amino-3,5-dimethoxybenzyl)-pyrimidine.
4. A composition according to claim 1, wherein the weight ratio of sul-phonamide to sulphonamide potentiator amounts to 5:1.
5. A process for the manufacture of an antibacterial composition as claimed in claim 1 which process comprises mixing together the sulphonamide of formula I given in claim 1,or a physiologically acceptable salt thereof with a strong base, and a sulphonamide potentiator as defined in claim 1, to produce a composition in which the weight ratio of sulphonamide to sulphonamide potentiator amounts to from 1:1 to 40:1.
6. A process according to claim 5 wherein the sulphonamide and the sul-phonamide potentiator are mixed together in a weight ratio of 5:1.
7. A pharmaceutical preparation which contains the sulphonamide of the formula (I) or a physiologically acceptable salt thereof with a strong base and a sulphon-amide potentiator as defined in claim 1, in a weight ratio of sulphonamide to sulphonamide potentiator of from 1:1 to 40:1, together with a compatible phar-maceutical carrier material.
8. A process for the manufacture of a pharmaceutical preparation as claimed in claim 7, which process comprises mixing an antibacterial composi-tion as set forth in claim 1 or the individual ingredients thereof with a com-patible pharmaceutical carrier material.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1740073 | 1973-12-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1043257A true CA1043257A (en) | 1978-11-28 |
Family
ID=4425118
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA215,752A Expired CA1043257A (en) | 1973-12-12 | 1974-12-11 | Antibacterially active combinations |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US3996357A (en) |
| JP (1) | JPS5089515A (en) |
| AT (1) | AT337890B (en) |
| BE (1) | BE823196A (en) |
| BR (1) | BR7410316A (en) |
| CA (1) | CA1043257A (en) |
| CU (1) | CU34136A (en) |
| DD (1) | DD117604A5 (en) |
| DE (1) | DE2455370C3 (en) |
| DK (1) | DK530674A (en) |
| ES (1) | ES432780A1 (en) |
| FI (1) | FI296474A (en) |
| FR (1) | FR2254346B1 (en) |
| GB (1) | GB1448040A (en) |
| HU (1) | HU169086B (en) |
| IE (1) | IE40295B1 (en) |
| IL (1) | IL45756A (en) |
| LU (1) | LU71448A1 (en) |
| NL (1) | NL7413331A (en) |
| PH (1) | PH11019A (en) |
| SE (1) | SE418455B (en) |
| SU (1) | SU573118A3 (en) |
| ZA (1) | ZA746108B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4209513A (en) | 1974-02-14 | 1980-06-24 | Burroughs Wellcome Co. | Tablet formulation |
-
1974
- 1974-09-25 ZA ZA00746108A patent/ZA746108B/en unknown
- 1974-09-30 IL IL45756A patent/IL45756A/en unknown
- 1974-10-10 DK DK530674A patent/DK530674A/da unknown
- 1974-10-10 NL NL7413331A patent/NL7413331A/en unknown
- 1974-10-11 FI FI2964/74A patent/FI296474A/fi unknown
- 1974-10-22 CU CU34136A patent/CU34136A/es unknown
- 1974-11-22 DE DE2455370A patent/DE2455370C3/en not_active Expired
- 1974-11-27 PH PH16572A patent/PH11019A/en unknown
- 1974-12-03 US US05/529,179 patent/US3996357A/en not_active Expired - Lifetime
- 1974-12-06 IE IE2528/74A patent/IE40295B1/en unknown
- 1974-12-10 FR FR7440504A patent/FR2254346B1/fr not_active Expired
- 1974-12-10 DD DD182905A patent/DD117604A5/xx unknown
- 1974-12-10 JP JP49141245A patent/JPS5089515A/ja active Pending
- 1974-12-10 LU LU71448A patent/LU71448A1/xx unknown
- 1974-12-10 SE SE7415493A patent/SE418455B/en unknown
- 1974-12-10 BR BR10316/74A patent/BR7410316A/en unknown
- 1974-12-11 HU HUHO1753A patent/HU169086B/hu unknown
- 1974-12-11 CA CA215,752A patent/CA1043257A/en not_active Expired
- 1974-12-11 BE BE151366A patent/BE823196A/en unknown
- 1974-12-11 ES ES432780A patent/ES432780A1/en not_active Expired
- 1974-12-11 GB GB5355574A patent/GB1448040A/en not_active Expired
- 1974-12-12 SU SU7402083724A patent/SU573118A3/en active
- 1974-12-12 AT AT990274A patent/AT337890B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| BE823196A (en) | 1975-06-11 |
| DE2455370B2 (en) | 1979-06-07 |
| DE2455370C3 (en) | 1980-02-07 |
| FR2254346B1 (en) | 1978-02-03 |
| NL7413331A (en) | 1975-06-16 |
| CU34136A (en) | 1977-03-08 |
| FR2254346A1 (en) | 1975-07-11 |
| IE40295B1 (en) | 1979-04-25 |
| DK530674A (en) | 1975-08-18 |
| SE418455B (en) | 1981-06-09 |
| AU7390774A (en) | 1976-04-08 |
| HU169086B (en) | 1976-09-28 |
| ES432780A1 (en) | 1976-12-16 |
| GB1448040A (en) | 1976-09-02 |
| SE7415493L (en) | 1975-06-13 |
| JPS5089515A (en) | 1975-07-18 |
| DD117604A5 (en) | 1976-01-20 |
| PH11019A (en) | 1977-10-25 |
| ZA746108B (en) | 1975-12-31 |
| BR7410316A (en) | 1976-06-22 |
| US3996357A (en) | 1976-12-07 |
| ATA990274A (en) | 1976-11-15 |
| AT337890B (en) | 1977-07-25 |
| FI296474A (en) | 1975-06-13 |
| IL45756A (en) | 1977-05-31 |
| IL45756A0 (en) | 1974-11-29 |
| SU573118A3 (en) | 1977-09-15 |
| DE2455370A1 (en) | 1975-06-19 |
| LU71448A1 (en) | 1976-11-11 |
| IE40295L (en) | 1975-06-12 |
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